Cell membranes are unique two dimensional solutions of specialized lipids and polypeptides. The overall aim of this program is the development of a quantitative understanding of the micro-fluid environment within membranes. The hydrophobic structure of the interior of the membrane will be related to the specific physico-chemical attributes of the individual constituents. The electrical properties of the bilayer will be systematically related to the nature of the hydrophobic interactions within the thin membrane. Planar lipid bilayers will be formed from mixtures of pure lipids. The membrane specific geometrical capacitance will be measured and related to the lipid partial molar volume, area/molecule and dielctric constant. The mixing of lipids of different acyl chain length within the membrane will be compared to their miscibility in bulk solutions. The intramembrane mixing of phospholipids, cholesterol and glycerides will be analyzed in the context of Regular Solution Theory. The modification of the membrane apolar region by local anesthetics will be studied in detail. Slightly polar anesthetics such as benzyl alcohol will be used to alter the intramembrane dielectric constant. Changes in lipid packing in the presence of anesthetics will also be studied. Anesthetic oil/water and oil/membrane partition coefficients will be measured. Gramacidin-A transmembrane channels will be inserted into membranes of precisely known lipid composition. Channel association and dissociation rates will be related to both lipid/peptide hydrophobic interactions and to membrane tension changes. De-stabilization of the ion channel by membrane swelling apolar compounds such as n-alkanes will be studied in detail in pure phospholipid bilayers. The anesthetic effects of alkanes will be compared to more polar agents such as benzyl alcohol.